The present invention provides novel compounds of formula I: ##STR2## which are pharmacologically useful as cardiovascular agents and, particularly, as antihypertensive, anti-anginal and calcium channel blocking agents with minimal adverse cardiac effects.
The invention further relates to novel pharmaceutical compositions comprising one or more of the active compounds of the invention utilized in conjunction with suitable pharmaceutical carriers as well as methods of using such compounds and pharmaceutical compositions thereof in the treatment, prophylaxis, or mitigation of cardiovascular diseases or conditions, such as hypertension and angina.
The compounds of formula I comprise substituted phenylacetonitrile (or benzeneacetonitrile) derivatives wherein an alkyl aminoalkylene chain is attached to the carbon atom bearing the cyano function and the amino group thereof is substituted by a hydrogenated bicyclic aromatic substituent. The hydrogenated bicyclic aromatic substituent characterizing the compounds of formula I represents a major departure from previously suggested phenylacetonitrile derivatives which require the presence of a phenyl (or substituted phenyl) alkyl amino group as the moiety on the right side of the molecule.
For example, U.S. Pat. No. 3261859 discloses .alpha.[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy -.alpha.-(1-methylethyl)hydrochloride) (i.e., verapamil hydrochloride) as a coronary vasodilator.
U.S. Pat. No. 4438131 discloses diphenyl-azaalkane derivatives of the formula: ##STR3## in which R.sub.1, R.sub.2, R.sub.3, R.sub.6, R.sub.7, and R.sub.8 are identical or different and selected from hydrogen, halogen, hydroxyl, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, nitro, C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 alkyl mercapto and radicals in adjacent positions can together form methylenedioxy, ethylenedioxy, or 1,3 dioxatetramethylene groups; R.sub.4 is straight-chain or branched-saturated or unsaturated alkyl of 9 to 20 carbon atoms, R.sub.5 is hydrogen or C.sub.1 -C.sub.4 alkyl and salts thereof. Anipamil[2-(3-methoxyphenyl)-2-[3-[N-[2-(3-methoxyphenyl)ethyl]methylamino ]propyl]tetradecanenitrile)] is disclosed within the foregoing patent and has subsequently been found to possess calcium ion antagonist activity analogous to verapamil hydrochloride.